2025 CONVENTION
■Background & Aims: Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, plays a critical role in various diseases. However, its detection in chronic liver disease models, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), is limited by the lack of universal markers and in vivo sensors. ■Methods: We utilized a near-infrared (NIR) fluorescent probe (TM) to monitor ferroptosis in MASLD models, both in vitro and in vivo. ■Results: TM exhibited viscosity-dependent turn-on fluorescence, enabling sensitive visualization of lipid peroxidation in ferroptotic hepatocytes and liver tissues, with higher sensitivity than BODIPY 581/591 C11. TM sensitively detected ferroptosis induced by RSL3 in AML12 cells, and this signal was also observed to decrease upon treatment with deferoxamine. Furthermore, TM was able to detect ferroptosis in liver tissues across multiple mouse in vivo models, including CCl₄-induced liver injury, Methionine- and Choline-Deficient Diet (MCD), and Choline-Deficient, L-Amino Acid-Defined, High-Fat Diet (CDAHFD) models. TM’s low toxicity and robust NIR signal permitted real-time in vivo imaging of ferroptosis in liver injury and MASLD models. ■Conclusions: TM enables sensitive detection and monitoring of ferroptosis in MASLD, providing a promising approach for early diagnosis of Metabolic Dysfunction-Associated Steatohepatitis (MASH).